VIRAL COFACTORS IN HIV INFECTION

我们建议研究致病的病毒决定因素 人类免疫缺陷病毒（HIV）。 有大量 分子、病毒学和流行病学证据表明， 辅因子，特别是EB病毒（EBV）、B型肝炎病毒 (HBV)，和巨细胞病毒（CMV），可能参与了 艾滋病相关综合征（ARC）与艾滋病的发病机制。 我们 因此，计划研究这些病毒与艾滋病毒的关系 感染的细胞，以确定是否存在辅因子关系， vivo. 我们计划进行原位杂交和免疫组织化学 艾滋病病毒感染者的组织和细胞染色 血清反应阳性，有ARC，有AIDS，还有对照组。 我们 目的是确定表达HIV的细胞是否也 显示EBV、HBV或CMV表达或边界细胞或此类细胞。 大量的淋巴组织，骨髓，大脑， 外周血淋巴细胞将使用组合的 原位杂交技术检测HIV RNA， 免疫组织化学染色检测HIV RNA， 免疫组织化学染色检测EBV、HBV或CMV 抗原;此外，还将使用结合 原位杂交检测CMV或HBV RNA， 免疫组织化学染色检测HIV表达 抗原的 在没有机会性感染的人身上 感染，CMV、HBV或EBV在相同细胞中表达，或 与那些表达HIV的细胞相邻的细胞将增加体内证据， 已经存在的体外证据表明这些病毒可能会 作为艾滋病毒感染进展的辅助因素。 此外，我们还将进行一系列实验， CMV或EBV是否可以增强HIV的产生， 体外 如果证明了体外增强作用，我们将测试 看看这种作用是否可以被抑制CMV的药物阻断， EBV复制。

We propose to investigate the viral determinants of pathogenesis by the human immunodeficiency virus (HIV). There is abundant molecular, virologic, and epidemiologic evidence that viral cofactors, particularly Epstein-Barr virus (EBV), hepatitis B virus (HBV), and cytomegalovirus (CMV), may be involved in the pathogenesis of AIDS related complex (ARC) and AIDS. We therefore plan to examine the relationship of these viruses to HIV infected cells to determine if a cofactor relationship may exist in vivo. We plan to perform in situ hybridization and immunohistochemical staining on tissues and cells from individuals who are HIV seropositive and well, have ARC, have AIDs, and controls. We aim to determine if cells demonstrating expression of HIV also show expression of EBV, HBV, or CMV or border or such cells. Numerous samples of lymphoid tissue, bone marrow, brain, and peripheral blood lymphocytes will be examined using the combined technique of in situ hybridization to detect HIV RNA and immunohistochemical staining to detect HIV RNA and immunohistochemical staining to detect EBV, HBV, or CMV antigen; in addition tissues will be examined using combined in situ hybridization to detect CMV or HBV RNA and immunohistochemical staining to detect expression of HIV antigen. In tissues derived from people without opportunistic infections, expression of CMV, HBV, or EBV in the same cells or cells neighboring those expressing HIV will add in vivo evidence to the already existing in vitro evidence that these viruses may act as cofactors in the progression of HIV infection. In addition, we shall perform a series of experiments to assay whether CMV or EBV can potentiate the production of HIV in vitro. If in vitro potentiation is demonstrated, we shall test to see if this effect can be blocked by agents that inhibit CMV or EBV replication.